Clinical Trial Results:
Tolerability and safety evaluation of the administration of Ig VENA at high infusion rates. Open label phase III study.
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Summary
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EudraCT number |
2013-000961-36 |
Trial protocol |
DE IT |
Global end of trial date |
31 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Aug 2016
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First version publication date |
07 Aug 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
KB057
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Kedrion S.p.A.
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Sponsor organisation address |
Località Ai Conti, Barga, Lucca, Italy, 55051
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Public contact |
Chiara Guarnieri, Kedrion SpA, 0039 0583767320, c.guarnieri@kedrion.com
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Scientific contact |
Chiara Guarnieri, Kedrion SpA, 0039 0583767320, c.guarnieri@kedrion.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluation of tolerability and safety of Ig VENA administered at high infusion rates
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Protection of trial subjects |
According to the study protocol:
"Each infusion will be conducted at an increasing rate as follows:
• 20/30 minutes at 1 ml/kg/hr,
• 20/30 minutes at 2 ml/kg/hr,
• 20/30 minutes at 4 ml/kg/hr,
• 20/30 minutes at 6 ml/kg/hr,
• Until the end of the infusion at 8 ml/kg/hr
The rate of infusion will be increased only if the patients did not present side effects in the previous infusion speed.
For AEs that occur during infusion, the following data will be recorded:
- infusion rate in effect at the time of AE onset,
- time of onset of AEs and
- time of AEs change materially in intensity and/or resolve
If an infusional AE occurs during the infusion, the study staff will decrease the infusion rate every 15 minutes until a rate at which symptoms have subsided is reached. Should the reaction become intolerable, the infusion will be stopped. The subject will exit the study and go back to the treatment schemes adopted and tolerated before his entrance in the study.
In case of Adverse Event, patients will be managed according to the instructions given in the product SmPC and standard practice at the site".
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
30 Jan 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Italy: 37
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Worldwide total number of subjects |
43
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EEA total number of subjects |
43
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
43
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||
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Pre-assignment period milestones
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Number of subjects started |
43 | ||||||||||
Number of subjects completed |
43 | ||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Single arm | ||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Ig VENA
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dosage
ID patients
0.2-0.8 g/kg (as reported in the SmPC). Subjects had to receive a total of 3 infusions of the IMP according to
their treatment scheme (every 3 or 4 weeks ± 4 days) as follows:
3-week scheme:
- Week 0/Infusion 1 (day 0);
- Week 3/Infusion 2 (day 21 ± 4)
- Week 6/Infusion 3 (day 42 ± 4)
4-week scheme:
- Week 0/Infusion 1 (day 0);
- Week 4/Infusion 2 (day 28 ± 4)
- Week 8/Infusion 3 (day 56 ± 4)
ITP patients
The two alternative treatment schedules reported in the SmPC were allowed:
0.8-1 g/kg given on day 1; this dose could be repeated once within 3 days, or
0.4 g/kg given daily for 2 to 5 days.
Method of administration
Infusions started at an initial rate of 1 ml/kg/hr for 20 minutes. If well tolerated, the rate of administration could
be increased to a maximum rate of 8 ml/kg/hr (2 ml/kg/hr; 4 ml/kg/hr; 6 ml/kg/hr; 8 ml/kg/hr) at 20/30 minutes
intervals (depending on dosage and/or body weight the patient could not reach the maximum infus
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
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Subject analysis sets
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety population included all enrolled patients who received the first infusion of IMP
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End points reporting groups
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Reporting group title |
Single arm
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Reporting group description |
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety population included all enrolled patients who received the first infusion of IMP
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End point title |
Verify that Ig VENA can be administered at higher infusion speed than for current SPC [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Evaluations during all study period
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical Analysis conducted was descriptive only and for this reason we cannot fill in the fields related to this issue |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
AEs reporting during all study period
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
All population (safety)
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0.42% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Nov 2013 |
Protocol Amendment No. 1 was generated following requests of Ethic Committees from Germany (Hannover EC), and updated the study period, gave further specifications on exclusion of patients unable to provide the informed consent, and added the SF-36v2 Quality of Life Questionnaire both at Screening and Follow-up visits for ID and ITP patients.
This Amendment was approved by German CA only (not by Italian CA) |
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19 Dec 2013 |
Protocol Amendment No. 2 was generated following requests of the Italian Health Authority (AIFA), and updated the study period, gave further specifications on the objectives of the study, on inclusion/exclusion criteria, on dosage and mode of administration of the IMP, added the SF-36 questionnaire, and corrected some other minor items on statistics, management of adverse events and references (some of changes above reported were the same requested from German EC and included in the Protocol Amendment 1 |
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14 Nov 2014 |
Protocol Amendment No. 3 was generated following requests of Ethic Committe from Germany (Hannover EC) and from German CA (PEI), and updated the Statistical Analysis Plan (attached to the Study Protocol). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
